Hexamethylenetetramine → 3-(4-Formyl-benzooxazol-2-yl)-benzoic acid methyl ester

Reaction equation

[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19]Br)[C:13]=3[N:14]=2)[CH:5]=1.C1N2CN3CN(C2)CN1C3.C(O)(=[O:34])C.O>>[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][CH:16]=[C:15]([CH:19]=[O:34])[C:13]=3[N:14]=2)[CH:5]=1

Participants

Reactant 3

HCID 4101Hexamethylenetetramine

HCID 21899381Acetic acid--water (1/1)

HCID 672793503-(4-Bromomethyl-benzooxazol-2-yl)-benzoic acid methyl ester

Product 1

HCID 860661063-(4-Formyl-benzooxazol-2-yl)-benzoic acid methyl esterYield 32%

Procedure

The crude 3-(4-bromomethyl-benzooxazol-2-yl)-benzoic acid methyl ester is treated with HMTA (1.8 mmol) in acetic acid/H2O (3 mL/1.5 mL) in a microwave oven at 130° C. for 20 minutes. The solvent is removed and the mixture is purified by silica gel chromatography (10-20% EtOAc/hexane) to yield 3-(4-formyl-benzooxazol-2-yl)-benzoic acid methyl ester as a white solid. Yield: 32%. 1H NMR (400 MHz, CDCl3) 10.8 (s, 1H), 8.97 (s, 1H), 8.53 (d, J=7.8 Hz, 1H), 8.26 (d, J=7.8 Hz, 1H), 7.94 (dd, J1=7.7 Hz, J2=1 Hz, 1H), 7.86 (d, J=8.1 Hz, 1H), 7.66 (t, J=7.8 Hz, 1H), 7.51 (t, J=7.9 Hz, 1H), 4.0 (s, 3H). LC/MS (ES+): (M+1) 282.1, (M+Na) 304.1.